Objective As biocatalysts, halohydrin dehalogenases can catalyze both cyclization and ring-opening reactions and are widely used in the synthesis of chiral epoxides and other compounds. The eco-friendly and efficient preparation of halohydrin dehalogenases is thus of great significance. In this study, we optimized the N-terminus of the coding sequence of the halohydrin dehalogenase HheC based on the mRNA secondary structure to achieve the efficient expression of this enzyme and then applied this enzyme in the synthesis of chiral epichlorohydrin. Methods The mRNA prediction tools was used to predict the secondary structure and thermodynamic properties of 5′mRNA. To reduce the stability of the mRNA secondary structure and increase folding free energy (ΔG), we designed the 5′mRNA sequence without changing the amino acid sequence. Furthermore, we characterized the expression efficiency and catalytic performance of this enzyme. Results The HheC mutant was obtained via the design of the 5′mRNA sequence, with the protein level increasing from 16.71% to 33.39% and the relative activity towards 1,3-dichloro-2-propanol increasing by three folds. Conclusion The optimization based on the secondary structure of 5′mRNA improves the expression level of HheC and enhances the synthesis efficiency of the target product, laying a foundation for constructing the route of enzymatic catalytic synthesis of chiral epichlorohydrin.